Acute ischemic stroke is the third leading cause of death in the United States and the leading cause of adult disability. The direct and indirect costs of stroke care exceed $51 billion annually. In 1996, the US Food and Drug Administration approved the first treatment for acute ischemic stroke, intravenous tissue plasminogen activator. Later that year, the National Institute of Neurologic Disorders and Stroke (a branch of the National Institutes of Health) convened a consensus conference on the Rapid Identification and Treatment of Acute Ischemic Stroke, setting goals for stroke care in the United States. Since then, it has become imperative that emergency physicians understand the pathophysiology of stroke, the basis and rationale for treatment, and the therapeutic approaches. This article reviews the state of the art of acute stroke treatment, its foundation, as well as its future.